GPR3 p.Ser328Arg

Variant names:

• chr1-27394780-A-C
• NM_005281.4:c.982A>C
• GPR3 p.Ser328Arg

Your query was ambiguous. Multiple possible variants found:

• chr1-27394780-A-C
• chr1-27394782-T-A
• chr1-27394782-T-G
• chr1-27394780-AGT-CGC
• chr1-27394780-AGT-CGA
• chr1-27394780-AGT-CGG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_005281.4(GPR3):​c.982A>C​(p.Ser328Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GPR3 NM_005281.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.05
• Publications: 0 publications found

Genes affected

GPR3 (HGNC:4484): (G protein-coupled receptor 3) This gene is a member of the G protein-coupled receptor family and is found in the cell membrane. G protein-coupled receptors, characterized by a seven transmembrane domain motif, are involved in translating outside signals into G protein mediated intracellular effects. The encoded protein activates adenylate cyclase and modulates amyloid-beta production in a mouse model, suggesting that it may play a role in Alzheimer's disease. [provided by RefSeq, Oct 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity GPR3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37712044).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005281.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR3	NM_005281.4	MANE Select	c.982A>C	p.Ser328Arg	missense	Exon 2 of 2	NP_005272.1	F1DAM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR3	ENST00000374024.4	TSL:1 MANE Select	c.982A>C	p.Ser328Arg	missense	Exon 2 of 2	ENSP00000363136.3	P46089
	GPR3	ENST00000924879.1		c.982A>C	p.Ser328Arg	missense	Exon 2 of 2	ENSP00000594938.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.097	D
MutationAssessor	Benign	2.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.36
Mutation Taster		=61/39	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-27721284;